Molecular alterations in AKT1, AKT2 and AKT3 detected in breast and prostatic cancer by FISH

被引:43
作者
Kirkegaard, Tove [1 ,2 ,3 ]
Witton, Caroline J. [2 ]
Edwards, Joanne [1 ]
Nielsen, Kirsten Vang [2 ]
Jensen, Linda Boye [1 ]
Campbell, Fiona M. [1 ]
Cooke, Timothy G. [1 ]
Bartlett, John M. S. [1 ]
机构
[1] Glasgow Royal Infirm, Dept Surg, Endocrine Canc Grp, Div Canc Sci & Mol Pathol, Glasgow G4 0SF, Lanark, Scotland
[2] Dako Denmark AS, Glostrup, Denmark
[3] Danish Canc Soc, Dept Tumour Endocrinol, Inst Canc Biol, Copenhagen, Denmark
关键词
AKT; breast cancer; FISH; genetic alterations; prostate cancer; ESTROGEN-RECEPTOR-ALPHA; PROTEIN-KINASE B/AKT; TRASTUZUMAB RESISTANCE; OVARIAN-CANCER; UP-REGULATION; PTEN; PATHWAY; ACTIVATION; GENE; PHOSPHORYLATION;
D O I
10.1111/j.1365-2559.2009.03467.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Molecular alterations in AKT1, AKT2 and AKT3 detected in breast and prostatic cancer by FISH Aims: The AKT family is implicated in cancer progression. There are three mammalian AKT isoforms located on chromosomes 14, 19 and 1, respectively. The aim of the study was to investigate genetic alterations of AKT in breast and prostatic cancers using fluorescence in situ hybridization (FISH). Methods and results: In oestrogen receptor(ER)-positive breast carcinomas, AKT1 was deleted in five (4.8%) and amplified in one (1%) carcinoma. Deletions of AKT2 were seen in 19 (21.1%) cases. No AKT2 amplifications were identified. Ten (9.9%) AKT3 amplifications but no deletions were seen. In prostatic cancer, AKT1 was amplified in one carcinoma (2.6%). No genetic changes were observed for AKT2 and AKT3. High frequencies of aneusomy for all chromosomes were observed in breast and prostatic carcinomas. Conclusions: In breast cancer AKT3 amplifications and AKT1 and AKT2 deletions were seen, which, to our knowledge, have not been shown by FISH before. Although these two cohorts cannot be directly compared, only one AKT1 amplification was identified in prostatic carcinomas. This indicates differences in the genetic changes underlying development of breast and prostatic cancers. To evaluate further the role of genetic changes of AKT in breast cancer progression, a cohort of both ER+ and ER- patients should be evaluated.
引用
收藏
页码:203 / 211
页数:9
相关论文
共 50 条
[1]  
Arboleda MJ, 2003, CANCER RES, V63, P196
[2]   The PIK3CA gene is mutated with high frequency in human breast cancers [J].
Bachman, KE ;
Argani, P ;
Samuels, Y ;
Silliman, N ;
Ptak, J ;
Szabo, S ;
Konishi, H ;
Karakas, B ;
Blair, BG ;
Lin, C ;
Peters, BA ;
Velculescu, VE ;
Park, BH .
CANCER BIOLOGY & THERAPY, 2004, 3 (08) :772-775
[3]   Type 1 Receptor Tyrosine Kinase Profiles Identify Patients With Enhanced Benefit From Anthracyclines in the BR9601 Adjuvant Breast Cancer Chemotherapy Trial [J].
Bartlett, John M. S. ;
Munro, Alison ;
Cameron, David A. ;
Thomas, Jeremy ;
Prescott, Robin ;
Twelves, Chris J. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (31) :5027-5035
[4]   MOLECULAR ALTERATIONS OF THE AKT2 ONCOGENE IN OVARIAN AND BREAST CARCINOMAS [J].
BELLACOSA, A ;
DEFEO, D ;
GODWIN, AK ;
BELL, DW ;
CHENG, JQ ;
ALTOMARE, DA ;
WAN, MH ;
DUBEAU, L ;
SCAMBIA, G ;
MASCIULLO, V ;
FERRANDINA, G ;
PANICI, PB ;
MANCUSO, S ;
NERI, G ;
TESTA, JR .
INTERNATIONAL JOURNAL OF CANCER, 1995, 64 (04) :280-285
[5]   A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer [J].
Berns, Katrien ;
Horlings, Hugo M. ;
Hennessy, Bryan T. ;
Madiredjo, Mandy ;
Hijmans, E. Marielle ;
Beelen, Karin ;
Linn, Sabine C. ;
Gonzalez-Angulo, Ana Maria ;
Stemke-Hale, Katherine ;
Hauptmann, Michael ;
Beijersbergen, Roderick L. ;
Mills, Gordon B. ;
de Vijver, Marc J. van ;
Bernards, Rene .
CANCER CELL, 2007, 12 (04) :395-402
[6]   Loss of PTEN is associated with progression to androgen independence [J].
Bertram, Jerod ;
Peacock, James W. ;
Fazli, Ladan ;
Mui, Alice L. -F. ;
Chung, Stephen W. ;
Cox, Michael E. ;
Monia, Brett ;
Gleave, Martin E. ;
Ong, Christopher J. .
PROSTATE, 2006, 66 (09) :895-902
[7]   Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor [J].
Brunet, A ;
Bonni, A ;
Zigmond, MJ ;
Lin, MZ ;
Juo, P ;
Hu, LS ;
Anderson, MJ ;
Arden, KC ;
Blenis, J ;
Greenberg, ME .
CELL, 1999, 96 (06) :857-868
[8]   Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor α -: A new model for anti-estrogen resistance [J].
Campbell, RA ;
Bhat-Nakshatri, P ;
Patel, NM ;
Constantinidou, D ;
Ali, S ;
Nakshatri, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (13) :9817-9824
[9]   Regulation of cell death protease caspase-9 by phosphorylation [J].
Cardone, MH ;
Roy, N ;
Stennicke, HR ;
Salvesen, GS ;
Franke, TF ;
Stanbridge, E ;
Frisch, S ;
Reed, JC .
SCIENCE, 1998, 282 (5392) :1318-1321
[10]   Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene [J].
Chen, WS ;
Xu, PZ ;
Gottlob, K ;
Chen, ML ;
Sokol, K ;
Shiyanova, T ;
Roninson, I ;
Weng, W ;
Suzuki, R ;
Tobe, K ;
Kadowaki, T ;
Hay, N .
GENES & DEVELOPMENT, 2001, 15 (17) :2203-2208